Researchers discover neurons that precisely keep time in the primate brain

Groups of neurons that precisely keep time have been discovered in the primate brain by a team of researchers that includes Dezhe Jin, assistant professor of physics at Penn State University and two neuroscientists from the RIKEN Brain Science Institute in Japan and the Massachusetts Institute of Technology (MIT). "This research is the first time that precise time-keeping activities have been identified in recordings of neuron activity," Jin said. The time-keeping neurons are in two interconnected brain regions, the prefrontal cortex and the striatum, both of which are known to play critical roles in learning, movement, and thought control.

The timing of individual actions, like speaking, driving a car, or throwing a football, requires very precise control. Although the lives of humans and other primates are extremely dependent on this remarkable capability, surprisingly little has been known about how brain cells keep track of time. This new discovery, published this week in the Proceedings of the National Academy of Sciences, is an important step toward answering this fundamental question.

To make the discovery, Jin analyzed thousands of neural-activity recordings made by Naotaka Fujii, from RIKEN, who then was a postdoctoral researcher in the lab of Ann Graybiels, an institute professor at MIT. Jin developed the computational tools that enabled the discovery of the novel results to emerge from the team's vast data set.

"The key finding is that neurons in the prefrontal cortex and the striatum encode the time information associated with sensory cues," Jin explained. "Visual cues, for example, elicit a variety of responses in a particular population of neurons. We found that the brain is able to tell the passage of time from the visual cues because different neurons are active at different times. Most remarkably we found that there are neurons that are active at precise times after a particular visual cue, and these neurons act like clocks that mark time."

The team of researchers trained two macaque monkeys to perform a simple eye-movement task. After receiving a "go" signal, the monkeys were free to perform the task at their own speed. The researchers found that neurons in the prefrontal cortex and the striatum consistently fired at specific times after the "go" signal -- at 100 milliseconds, 110 milliseconds, 150 milliseconds, and other intervals. Like a stopwatch, these neurons provided a fine-scale coverage over a period of several seconds. The combined activity of these neurons provided "time stamps" that could specify any given time point with a remarkable precision of less than 50 milliseconds, which is more than sufficient to account for most behaviors.

"Another key finding of our work is that the brains of the monkeys constructed neural activities to encode time even though timing was not required for the experimental task," Jin said. "We suggest that time encoding is the essential function of the brain's neural networks."

Jin said this kind of time-keeping activity long had been suggested in theories of how animals learn to recognize a stimulus that leads to delayed rewards, but his team's work is the first experimental demonstration of this Time-keeping function using recordings of neuron activity.

The discovery opens the door to many investigations, including how the brain produces this time code, and how the time code is used to control behavior and learning. In the longer term, the ability to read the brain's natural time code may facilitate the development of neural prosthetic devices for conditions such as Parkinson's disease, in which neurons in the prefrontal cortex and basal ganglia are disrupted and the ability to control the timing of movements is impaired.